The production of isochromans has been shown in the art and certain novel isochromans have recently been disclosed with an outstanding musk fragrance. Such isochromans especially adapted for perfumery by virtue of their fragrance properties have been disclosed in Heeringa & Beets U.S. Pat. No. 3,360,530, issued on Dec. 26, 1967.
A number of routes are available for the production of isochromans, such as those set forth in U.S. Pat. No. 3,360,530 and one of the most straightforward of these routes is treatment of a Friedel-Crafts reactant with an alkylene oxide under Friedel-Crafts conditions to form an aryl alkanol. The aryl alkanol is then isolated and thereafter reacted with formaldehyde to cyclialkylate the alcohol. The efficiency of this multi-stage process leaves much to be desired because of a number of discreet processing steps and extended working times which also results in considerable yield impairment.
U.S. Pat. No. 3,532,719 sets forth a process for producing such isochromans which solved a number of the problems of the processes set forth in U.S. Pat. No. 3,360,530. U.S. Pat. No. 3,532,719 provided a more simplified and more economical process for producing isochromans which comprises reacting a Friedel-Crafts reactant with an alkylene oxide in the presence of aluminum chloride in a chlorinated hydrocarbon solvent to form, in situ, an aryl alkanol-aluminum chloride complex; partially deactivating the aluminum chloride after formation of the aryl alkanol complex; and cyclialkylating the contained aryl alkanol with formaldehyde or a formaldehyde equivalent in the presence of the partially deactivated aluminum chloride to form, upon quenching, the isochroman. The disadvantage of such procedures for the preparation of isochromans is the use of halogenated hydrocarbon solvents, many of which are expensive and have been reported to be health hazards. The use of halogenated benzene derivatives require very low temperatures -40.degree. C. to -30.degree. C. in order to obtain the best yields. The maintenance of such low temperatures for an extremely exothermic reaction requires the installation of expensive processing equipment and extended reaction times, which can impair yields.
Steyn and Holzapfel, Tetrahedron, 23 4449 (1967), reports the reaction of a halo aryl alkanol with chloromethyl methyl ether and zinc chloride to give an isochroman according to the following reaction: ##STR1##
Meyer and Turner, Tetrahedron, 27 2609 (1971), reports the reaction of a methoxy aryl alkanol with sodium hydride and chloromethyl methyl ether to give a methoxy aryl alkanol methyl ether. Subsequent treatment of the methoxy aryl alkanol methyl ether with toluenesulfonic acid is indicated to yield isochromans according to the following reaction: ##STR2##
The disadvantages of such processes include the utilization of chloromethyl methyl ether which has been reported to be a health hazard. Also, several distinct processing steps are needed to form the isochroman ring, compared to the simplicity of a single processing step in the instant invention.
In order to overcome the problems of the prior art U.S. Pat. No. 3,910,964 issued on Oct. 7, 1975 and U.S. Pat. No. 3,978,090 issued on Aug. 31, 1976 covered a process for producing isochromans having the structure: ##STR3## wherein R.sub.1 and R.sub.2 are each (i) separately selected from the group consisting of hydrogen, lower alkoxy, lower alkyl, and, (ii) taken together, selected from the group consisting of benzo, cyclopentano, cyclohexano, naphtho, monoalkyl cyclopentano, polyalkyl cyclopentano, monoalkyl cyclohexano and polyalkyl cyclohexano, and R.sub.3 and R.sub.4 are the same or different and are selected from the group consisting of hydrogen and lower alkyl comprising the steps of intimately admixing:
(A) An alkanol having the structure: ##STR4##
(B) An acetal having the structure: ##STR5## (wherein R.sub.5 and R.sub.6 are alkyl;
(C) A protonic acid selected from the group consisting of p-toluene sulfonic acid and phosphoric acid; and
(D) An azeotroping agent selected from the group consisting of n-hexane, cyclohexane, methyl cyclohexane, benzene and toluene; and simultaneously (i) heating the resulting mixture of a period of time whereby a substantial amount of the isochroman having the above structure is formed while (ii) azeotropically removing water of reaction with the azeotroping agent.
However, the processes of U.S. Pat. Nos. 3,910,964 and 3,978,090 require isolation of the aryl alkanol resulting from the Friedel-Crafts reaction, and subsequent conversion, in a separate step, to the cyclialkylated isochroman. These two step processes require significantly more processing time and processing equipment compared to the efficient one step method of the instant invention.
Prior to the instant invention, synthetic musks such as 5-acetyl-1,1,2,3,3,6-hexamethylindane having the structure: ##STR6## and 6-acetyl-1,1,3,4,4,6-hexamethyltetrahydronaphthalene were produced using several complicated and low-yield processes. Arctander, "Perfume and Flavor Chemicals (aroma chemicals)" published by the author in 1969, volume I, Monographs numbers 40 and 41 discloses such acylated indane musks.
The use of six, seven or eight carbon saturated hydrocarbons as solvents in order to aid Friedel-Crafts catalysis is disclosed at column 3, lines 5-10 of the U.S. Pat. No. 3,439,056 but the nature of the reaction (conversion of a first type of acylcyclic compound to a second type of acylcyclic compound using a specific catalyst) is different in kind from the reaction of the instant invention.